Which of the following drug for moderate-to-severe psoriasis inhibits both IL-12 and IL-23?
First, I need to recall the biologics used in psoriasis. The key ones are TNF-alpha inhibitors like adalimumab, etanercept, infliximab. Then there are IL-12/23 inhibitors, IL-23 inhibitors, and IL-17 inhibitors. The question specifically mentions inhibiting both IL-12 and IL-23.
I remember that ustekinumab is a monoclonal antibody that targets the p40 subunit shared by both IL-12 and IL-23. That makes sense because IL-12 is composed of p35 and p40 subunits, and IL-23 has p19 and p40. By blocking p40, ustekinumab inhibits both cytokines.
Other drugs like secukinumab target IL-17, and guselkumab or risankizumab target IL-23 specifically. So if the options include ustekinumab, that's the correct answer. The other options would be TNF-alpha inhibitors or IL-23 alone inhibitors.
So the core concept here is understanding the cytokine pathways in psoriasis and the specific biologics that target them. The correct answer is ustekinumab. The wrong options would be other biologics that don't target both IL-12 and IL-23. The clinical pearl is that ustekinumab is the only one that inhibits both by targeting the shared p40 subunit.
**Core Concept**
This question tests knowledge of biologic therapies for psoriasis, specifically their mechanisms of action. IL-12 and IL-23 are pro-inflammatory cytokines critical in psoriasis pathogenesis, with IL-23 being a key driver of Th17 cell activation and keratinocyte proliferation.
**Why the Correct Answer is Right**
Ustekinumab is a human monoclonal antibody that targets the **p40 subunit shared by IL-12 and IL-23**. By inhibiting both cytokines, it reduces Th1 and Th17 immune responses, which are central to psoriatic inflammation. This dual inhibition distinguishes it from other biologics like IL-23-specific agents (e.g., guselkumab) or IL-17 inhibitors (e.g., secukinumab).
**Why Each Wrong Option is Incorrect**
**Option A:** TNF-alpha inhibitors (e.g., adalimumab) block TNF, not IL-12/23, and have no effect on these cytokines.
**Option B:** IL-17 inhibitors (e.g., ixekizumab) target IL-17, a downstream mediator, not IL-12/23.
**Option C:** IL-23-specific inhibitors (e.g., tildrakizumab) block only IL-23, not IL-12.
**Option D:** Phosphodiester